Objectives: Adaptive interaction with the environment requires the ability to predict both human and non-biological motion trajectories. Prior accounts of the neurocognitive basis for prediction of these two motion classes may generally be divided into those that posit that non-biological motion trajectories are predicted using the same motor planning and/or simulation mechanisms used for human actions, and those that posit distinct mechanisms for each. Using brain lesion patients and healthy controls, this study examined critical neural substrates and behavioral correlates of human and non-biological motion prediction. Methods: Twenty-seven left hemisphere stroke patients and 13 neurologically intact controls performed a visual occlusion task requiring prediction of pantomimed tool use, real tool use, and non-biological motion videos. Patients were also assessed with measures of motor strength and speed, praxis, and action recognition. Results: Prediction impairment for both human and non-biological motion was associated with limb apraxia and, weakly, with the severity of motor production deficits, but not with action recognition ability. Furthermore, impairment for human and non-biological motion prediction was equivalently associated with lesions in the left inferior parietal cortex, left dorsal frontal cortex, and the left insula. Conclusions: These data suggest that motor planning mechanisms associated with specific loci in the sensorimotor network are critical for prediction of spatiotemporal trajectory information characteristic of both human and non-biological motions. (JINS, 2017, 23, 171–184)